Pyrls Press — 2024

Type 2 Diabetes
Pharmacotherapy

More clinical pearls at pyrls.com

Scope of Document
This document contains a collection of concise resources on the subject of
glycemic-lowering pharmacotherapy for adult patients with type 2 diabetes. It is
intended to be utilized as a supplemental resource for learning and/or referencing,
and is not a comprehensive guide to all relevant information on the subject.

Disclaimer
Readers should note that this document was published in January 2024, and
some of the information in this document is subject to frequent change.

All information provided by Pyrls is intended for healthcare professionals and

students for educational purposes only and should only be used appropriately in
the context of the provider's legal role as a healthcare provider in their respective
state and country. Cosmas Health, Inc. does not accept responsibility or liability
for the application of this information in direct or indirect patient care, and such
information should not be substituted for the advice, diagnosis, or treatment of a
qualified health care professional. It is the responsibility of the healthcare
provider to ascertain the Food and Drug Administration status of each drug,
medical device, or standards of practice regarding procedures, and/or imaging
modalities used in their clinical practice. The editors and authors have made
every effort to provide accurate and complete information.

We thank you so much!

The Pyrls Team

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TABLE OF CONTENTS

Diagnostic Criteria and Screening for Type 2 Diabetes 1

Treatment Assessment and Goals 3

Estimated Average Glucose 4

Continuous Glucose Monitors (CGMs) 5

Comparison of CGMs 8

Overview of Hemoglobin A1C 10

T2DM Treatment Algorithm for Glycemic Control (2024 Update) 11

Insulin Classes and Action Profiles 13

Insulin Storage Requirements 14

Injection Areas 16

T2DM Drug Class Comparison 17

Diabetes Drugs: Cardiovascular and Renal Effects 18

Metformin: Dosing and Indications 20

GLP-1 RAs and GLP-1/GIP RA: Efficacy and Safety 21

GLP-1 RAs and GLP-1/GIP RA: Dosing and Indications 22

SGLT2 Inhibitors: Efficacy and Safety 25

SGLT2 Inhibitors: Dosing and Indications 26

TABLE OF CONTENTS (cont.)

DPP-4 Inhibitors: Efficacy and Safety 27

DPP-4 Inhibitors: Dosing and Indications 28

Sulfonylureas: Efficacy and Safety 29

Sulfonylureas: Dosing and Indications 30

Thiazolidinediones: Efficacy and Safety 32

Thiazolidinediones: Dosing and Indications 32

Drugs that Cause Hyperglycemia 33

Drugs that Cause Hypoglycemia 34

Hypoglycemia Classification and Treatment 35

References 36

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 Reference(s): 1

Diagnostic Criteria and Screening for Type 2 Diabetes

Diagnostic Criteria

CONDITION A1C (%) FPG* (mg/dL) 2-HR PG** (mg/dL)

Diabetes ≥6.5 ≥126 ≥200

Prediabetes 5.7 - 6.4 100 - 125 140 - 199

Recreated from Table 2.2 of the ADA Standards of Care in Diabetes - 2024
*Fasting plasma glucose (FPG) should be conducted after an 8+ hour fasting period
**Plasma glucose 2 hours after the administration of 75 grams of glucose during an oral glucose tolerance test (OGTT)

Tests used to diagnose diabetes include: hemoglobin A1C (A1C), fasting plasma
glucose (FPG) and 2-hour plasma glucose (2-HR PG) during an oral glucose
tolerance test.

The plasma glucose values (FPG and 2-HR PG) have greater diagnostic accuracy
than A1C in patients with discordant values (e.g., A1C value is not elevated but
FPG and/or 2-hour PG values are elevated).

However, A1C is more convenient than plasma glucose tests due to a lack of
required fasting. Additionally, since it is an indirect measure of average blood
glucose over a period of time (~3 months) it is less affected by glucose
fluctuations or disturbances (due to stress, diet changes, illness, etc.).

In cases where there is evidence of discordance between A1C and plasma glucose
values the A1C value must be considered unreliable. There are a number of
possible underlying causes or conditions for this discrepancy, such as sickle cell
disease, pregnancy and HIV. When an underlying cause is suspected or known,
only plasma glucose testing (FPG or 2-HR PG) may be used for diagnostic
purposes.

A diagnosis for diabetes requires two abnormal screening results (from the same
or separate samples using the same or different test). In cases of separate
samples it is recommended that the second test be performed as soon as
possible. In cases of discordant results (e.g. A1C 6.2% and FPG 175 mg/dL) the
test result above the diagnostic threshold should be repeated (in this example,
FPG). If the test results are near the diagnostic threshold, testing should be
repeated in 3-6 months.

The only times when two abnormal tests are not required are in cases where there
is clear clinical evidence of diabetes, such as classic symptoms of hyperglycemia/
hyperglycemic crisis (e.g. polydipsia, polyuria, blurred vision) plus a random
plasma glucose ≥200 mg/dL. In these cases, repeat testing is not required.

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 Reference(s): 1

Diagnostic Criteria and Screening for Type 2 Diabetes

Screening for Type 2 Diabetes
Screening should be considered for overweight/obese* adults with one or more
of the following risk factors:
• First-degree relative with diabetes
• High-risk race/ethnicity (e.g., African American, Latino, Native American,
Asian American, Pacific Islander)
• History of cardiovascular disease
• Hypertension (BP ≥130/80 mmHg or on antihypertensive therapy)
• HDL <35 mg/dL and/or triglycerides >250 mg/dL
• Polycystic ovary syndrome
• Physical inactivity
• Clinical conditions associated with insulin resistance (e.g., severe obesity, - -
- - - acanthosis nigricans)
*BMI ≥ 25 kg/m2 (or ≥ 23 kg/m2 in Asian American individuals)

Patients with prediabetes (A1C 5.7-6.4%) should be screened annually. Patients

with a history of gestational diabetes should be screened every 3 years. For all
other patients, screening for diabetes should begin at an age of 35 years and be
repeated at least every 3 years (if results are normal).

Certain medications (e.g., glucocorticoids, statins, thiazide diuretics) may

increase the risk for developing type 2 diabetes. It is reasonable to consider
screening patients receiving these medications for prediabetes and diabetes.

Patients prescribed second-generation antipsychotic medication should be

screened for prediabetes and diabetes at baseline, 12-16 weeks after initiation
(sooner, if indicated) and then annually thereafter.

Patients with HIV should be screened for prediabetes and diabetes at baseline
(prior to antiretroviral therapy) and when switching antiretroviral therapy (ART).
Screening should repeat 3-6 months after initiating or switching ART. If results are
normal, screening should continue annually. In these patients, FPG is the
recommended screening method.

Unless otherwise specified, FPG, 2-HR PG following 75 gram oral glucose

tolerance test or A1C can be used as appropriate screening methods.

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 Reference(s): 1

Treatment Assessment and Goals

Treatment Assessment

The primary metrics for monitoring treatment of type 2 diabetes (T2DM) are
hemoglobin A1C (A1C) and preprandial/postprandial glucose measurements.

In patients with diabetes, hemoglobin A1C and/or appropriate CGM metrics (e.g.,
time in range, time above/below range) should be assessed:
• At least twice yearly (e.g., every 6 months) in patients meeting their - - - - - -
- - - treatment goals and maintaining stable glycemic control. Those with - - - - -
- - - frequent/severe hypo- or hyperglycemia, those with fluctuating health and - -
- - - pediatric patients undergoing growth and development may require more - -
- - - frequent monitoring (e.g., every 3 months).
• At least quarterly (e.g., every 3 months) and as needed in patients with - - -
- - - recent therapy change, those not meeting their glycemic goals.

Preprandial and postprandial plasma glucose levels goals can help guide healthy
diet practices, lifestyle changes, and pharmacotherapy selection and dosing.

Treatment Goals
The primary goal of therapy is reducing the patient’s A1C to goal without causing
hypoglycemic episodes.

Treatment goals must be individualized (and periodically reassessed) after taking into
consideration comorbid conditions, hypoglycemia risk and other patient-specific
characteristics.

POPULATION A1C (%) PREPRANDIAL 1-HR PPG 2-HR PPG

Most patients* <7.0 80 - 130 mg/dL -- <180 mg/dL

Certain patients** <8.0 -- -- --

Pregnant*** <6.0 <95 mg/dL^ <140 mg/dL <120 mg/dL

Recreated from Tables 6.3 and Recommendations 6.7, 15.7 and 15.8 of the ADA Standards of Care in Diabetes - 2024
*More strict goals may be reasonable if achievable without significant hypoglycemia risk
**Those at risk of or prone to severe hypoglycemia, limited life expectancy, important comorbidities, long duration of diabetes, or patients who prefer a less
stringent A1C goal
***If A1C < 6% cannot be safely achieved, choosing a less strict goal of < 7% is reasonable to avoid hypoglycemic events
^Fasting plasma glucose

Deintensification of therapy for patients with A1C between 6-7% is not necessary
if the hypoglycemia risk is low. However, if the concern for hypoglycemia is
significant then deintensification may be warranted as any long-term treatment
benefit may be outweighed by the short-term risk.

Patients that are high-risk for hypoglycemia that are receiving hypoglycemia-
causing medication (e.g., insulin, sulfonylureas) should have said medication de-
intensified or switched to an agent with a lower-risk for hypoglycemia.

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 Reference(s): 1

Treatment Assessment and Goals (cont.)

Assessment & Modification Interval
The treatment regimen should be reassessed every 3-6 months and modified if
appropriate.

Generally, patients should be assessed every 3 months while not at target

glycemic goals and every 6 months while stable at goal. Treatment intensification
for patients not at goal should not be delayed when possible.

Estimated Average Glucose

The table below provides estimated average glucose levels (eAG) for specific A1C
values. This data can be used to counsel patients and guide therapy.

Patients are generally able to understand blood glucose values better than A1C. By
discussing treatment goals with patients while including target eAG they can better
understand their own glucose readings and overall glycemic control.

A1C (%) AVERAGE GLUCOSE (mg/dL)

5 97 (76 - 120)

6 126 (100 - 152)

7 154 (123 - 185)

8 183 (147 - 217)

9 212 (170 - 249)

10 240 (193 - 282)

11 269 (217 - 314)

12 298 (240 - 347)

Recreated from Table 6.1 from the ADA Standards of Care in Diabetes - 2024

For example, if a patient’s current A1C is 9.0% their eAG would be 212 mg/dL.
Typically, an A1C goal of < 7.0% is appropriate for most patients (eAG < 154 mg/dL).

Encouraging the patient to achieve an average glucose of < 154 mg/dL can better
enable them to track their own progress between office visits and A1C tests and
more clearly see the benefits of positive lifestyle modifications (e.g., dietary
changes, increased physical activity, weight loss).

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 Reference(s): 1

Continuous Glucose Monitors (CGMs)

Continuous glucose monitors (CGMs) have been shown to improve A1C levels,
time in range, and reduce hypoglycemia compared to standard blood glucose
monitoring (e.g., "fingerstick" monitoring) alone in many studies.

For managing diabetes, there are different types of CGMs available, and the
choice should depend on the individual's specific situation and preferences.
Patients who are prescribed CGMs should receive regular instruction and
evaluation of their CGM use, testing technique and glycemic management.

Most CGMs involve insertion of a small wire sensor under the skin on the back of
the upper arm (Senseonics Eversense E3 is implanted under the skin surgically).
Then a transmitter is used to deliver the glucose readings to a receiver or smart
device. For certain CGMs (such as the Freestyle Libre 2), the receiver/smart
device is actually used to intermittently scan the sensor and record the readings.

Blood Glucose Readings vs Sensor Glucose Readings

Patients using CGMs will occasionally check their blood glucose with a fingerstick
device.

Blood glucose readings are taken from your bloodstream, providing a direct
measurement of your current glucose levels.

Sensor glucose readings are obtained from the interstitial fluid, a fluid residing
just beneath the skin. When carbohydrates are consumed, the body absorbs
glucose into the bloodstream before it diffuses into the interstitial fluid.

This difference in the source of glucose readings causes there to be a time lag
between the two. This time lag forms the basis for CGM's ability to provide not only
current glucose readings but also an arrow indicating the direction in which
glucose levels are headed.

It is important to educate patients about the differences between blood glucose

and sensor glucose readings. Doing so helps them understand that these values
won't always align perfectly and can prevent patients from losing trust in their CGM
device due to perceived inconsistencies between the two readings.

The warm-up time for CGMs is not the same as the lag time, although they are
related concepts. The warm-up time refers to the initial period when a CGM sensor
is activated before it starts providing accurate and reliable glucose readings. The
duration of the warm-up time can vary depending on the specific CGM system but
typically ranges from 30 minutes to a few hours.

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 Reference(s): 1

Continuous Glucose Monitors (cont.)

Real-time CGMs vs Intermittently Scanned CGMs
Real-time CGMs (rtCGMs) and intermittently scanned CGMs (isCGMs) both
measure blood glucose levels continuously. However, isCGMs must be scanned in
order to view and store the glucose readings. rtCGMs, on the other hand, do not
require scanning (although being within range of the receiver/smart device is
necessary).

Per the American Diabetes Association (ADA) 2024 Standards of Care, the
following patient populations with diabetes should be offered CGMs:
• Patients receiving multiple daily insulin injections or a continuous - - - - - - - - -
- - - subcutaneous infusion
• Adults receiving basal insulin

The ADA gives a higher grade of recommendation for rtCGMs than isCGMs.

It is important to note, when used properly, CGMs may be beneficial for any patient
with diabetes, regardless of their A1C or medication regimen (e.g., insulin-
dependent or non-insulin dependent).

For maximum benefit, rtCGMs should be used as close to daily as possible. isCGMs
should be scanned at least once every 8 hours.

Please note: Blood glucose testing with a fingerstick device should be done if
diabetes symptoms or expected blood sugar levels do not match the results from a
CGM. This can help confirm unexpected blood sugar readings before making
treatment decisions.

Drugs that Interfere with CGM Readings

It is important to note that certain drugs can interfere with CGM readings, causing
glucose readings to be falsely high or low.

Blood glucose testing with a fingerstick device should be done if diabetes

symptoms or expected blood sugar levels do not match the results from a CGM.
This can help confirm unexpected blood sugar readings before making treatment
decisions.

DRUG AFFECTED DEVICES EFFECT

Acetaminophen (>4000 mg/day) Dexcom G6 and G7 Causes falsely high readings

Acetaminophen (any dose) Medtronic Guardian Causes falsely high readings

Vitamin C (>500 mg/day) Freestyle Libre Causes falsely high readings

Dexcom G6 and G7
Hydroxyurea Causes falsely high readings
Medtronic Guardian

Mannitol or sorbitol Senseonics Eversense Causes falsely high readings

(IV or as peritoneal dialysis solution)

Adapted from Table 7.4 of the ADA Standards of Care in Diabetes - 2024

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 Reference(s): 1

Continuous Glucose Monitors (cont.)

Standardized CGM Metrics and Recommendations
Although A1C presently serves as the predominant gauge for directing glucose
management and as a valuable indicator of the risk of developing diabetes-related
complications, the CGM metrics time in range (including time spent below and
above the target range) and glucose management indicator offer insights that can
inform a more individualized diabetes management strategy.

Time in range (TIR) has been determined to be a valuable measure for assessing
glycemic control and glucose patterns. Time above range (TAR) and time below
range (TBR) can be valuable indicators for adjusting insulin dosing and reassessing
the treatment strategy.

The table below provides an overview of standardized CGM metrics as well as

corresponding ADA recommendations.

METRIC DESCRIPTION RECOMMENDATIONS*

Time above range Percent of readings and time >250 mg/dL <5% for most adults
(TAR) (level 2 hyperglycemia) <10% for older adults

Percent of readings and time 181-250 mg/dL <25% for most adults
(level 1 hyperglycemia) <50% for older adults

Time in range Percent of readings and time 70-180 mg/dL >70% for most adults
(TIR)** >50% for older adults

Time below range Percent of readings and time 54-69 mg/dL <4% for most adults
(TBR)** (level 1 hypoglycemia) <1% for older adults

Percent of readings and time <54 mg/dL <1%

(level 2 hypoglycemia)

Glycemic variability Fluctuations in blood glucose levels ≤36%***

Glucose <7.0%
Estimate of A1C based on average CGM
management
readings for ≥ 14 days (for most patients)
indicator (GMI)

Adapted from Table 6.2 of the ADA Standards of Care in Diabetes - 2024
* Treatment goals must be individualized and take into consideration comorbid conditions, hypoglycemia risk and patient-specific characteristics
** A TIR >50% and TBR <1% is recommended for patients with frailty or a high risk for hypoglycemia
*** Certain studies state that targeting a lower glycemic variability (< 33%) offers an added layer of defense against hypoglycemia in individuals taking insulin or
sulfonylureas

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Comparison of Continuous Glucose Monitors Reference(s): Individual manufacturer product labeling

REAL-TIME READINGS SENSOR TRANSMITTER COVERED BY MEDICARE ''

Dexcom G7 Every 5 minutes Change every 10 days Transmitter integrated into sensor Yes

Dexcom G6* Every 5 minutes Change every 10 days Change every 3 months Yes

Senseonics Eversense E3 Every 5 minutes Subcutaneous implant Charge daily Yes

replaced every 6 months (full charge time of 15 minutes)

Freestyle Libre 3** Every 1 minute Change every 14 days Transmitter integrated into sensor Yes

Medtronic Guardian Every 5 minutes Change every 7 days Must be charged after each sensor No***
Connect use so that the battery lasts 7 days
(full charge time of up to 2 hours)

INTERMITTENTLY SCANNED READINGS SENSOR TRANSMITTER COVERED BY MEDICARE “

Freestyle Libre 2** Every 1 minute Change every 14 days N/A Yes
(scanning required)

*Compatible with Omnipod automated insulin delivery system

**Compatible with mylife Loop automated insulin delivery system
***Does not have a separate durable medical receiver for CGM (only works with app/smart device)
" Must meet Medicare coverage criteria, such as having a separate durable medical receiver for CGM

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Comparison of Continuous Glucose Monitors (cont.) Reference(s): Individual manufacturer product labeling

REAL-TIME APPROVED AGES WARM-UP TIME APPROVED APPLICATION SITES

Dexcom G7 2 years and older 30 minutes Back of upper arm

Dexcom G6 2 years and older 2 hours Abdomen and back of upper arm; upper buttocks (ages 2-17 years)

Senseonics Eversense E3 18 years and older 24 hours Back of upper arm (inserted surgically)

Freestyle Libre 3 4 years and older 1 hour Back of upper arm

Medtronic Guardian 14 to 75 years Up to 2 hours Abdomen and back of upper arm

Connect

INTERMITTENTLY SCANNED APPROVED AGES WARM-UP TIME APPROVED APPLICATION SITES

Freestyle Libre 2** 4 years and older 1 hour Back of upper arm

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 Reference(s): 1, 3

Overview of Hemoglobin A1C

Hemoglobin A1C Review

Before discussing the hemoglobin A1C (A1C) lab value itself, it is important to
understand the relationship between A1C and hemoglobin. Hemoglobin is an iron-
containing transport protein found in red blood cells. Over the lifespan of red blood
cells (~120 days) the hemoglobin protein becomes glycated (chemically linked to
sugar). The greater the concentration of glucose in the bloodstream, the greater
amount of hemoglobin becomes glycated. The A1C test is a measurement of the
percentage of glycated hemoglobin in the bloodstream.

Limitations of Hemoglobin A1C

It is important to note that hemoglobin A1C (A1C) is an indirect measure of a
patient’s average blood glucose levels. It does not provide information regarding
glycemic variability (i.e., the frequency of hyper- and hypoglycemia) which is why
assessing a collection of plasma glucose levels in addition to A1C is necessary to
most effectively evaluate glycemic control.

Additionally, hemoglobin abnormalities may falsely increase or decrease A1C lab

values. This should be considered when the reported A1C value(s) do not correlate
with the patient’s plasma glucose levels.

Conditions that may falsely increase A1C include:

• Anemia (due to iron, vitamin B12 and/or folic acid deficiency)
• Severe hypertriglyceridemia (> 1,750 mg/dL)
• Chronic alcohol consumption

Conditions that may falsely decrease A1C include:

• Acute or chronic blood loss
• Hemolytic anemia (e.g., sickle cell anemia, G6PD deficiency anemia)
• End-stage renal disease
• Pregnancy (screening should be performed using oral glucose tolerance test)

If suspected, the use of alternative measures of average glucose levels may be

warranted (e.g., fructosamine test).

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 Reference(s): 4-24

Insulin Classes and Action Profiles

BRAND GENERIC CLASS DURATION TYPE

Admelog Insulin lispro (conventional) Rapid-acting 4-6 hours Analog

Afrezza Inhaled insulin Rapid-acting 2.5-3 hours Human

Apidra Insulin glulisine Rapid-acting 5-6 hours Analog

Basaglar Insulin glargine Long-acting 24-30 hours Analog

Fiasp Insulin aspart (faster-acting) Rapid-acting 5-6 hours Analog

HumaLog Insulin lispro (conventional) Rapid-acting 4-6 hours Analog

Humulin N NPH Intermediate-acting 14-18 hours Human

Humulin R (U-100) Regular insulin Short-acting 6-8 hours Human

Humulin R (U-500) Regular insulin Intermediate-acting ~21 hours (13-24 hours) Human

Lantus Insulin glargine Long-acting 24-30 hours Analog

Levemir Insulin detemir Long-acting 20-24 hours Analog

Insulin lispro-aabc
Lyumjev (faster-acting) Rapid-acting 4-6 hours Analog

NovoLog Insulin aspart (conventional) Rapid-acting 5-6 hours Analog

Novolin N NPH Intermediate-acting 14-18 hours Human

Novolin R Regular insulin Short-acting 6-8 hours Human

Rezvoglar Insulin glargine-aglr Long-acting 24-30 hours Analog

Semglee Insulin glargine-yfgn Long-acting 24-30 hours Analog

Toujeo Insulin glargine Long-acting 24-30 hours Analog

Tresiba Insulin degludec Long-acting 36-42 hours Analog

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 Reference(s): 6-24

Insulin Storage Requirements

All products are good until their expiration date when kept unopened and
refrigerated (36°F-46°F [2°C-8°C]).

DAYS GOOD AT
BRAND GENERIC ROOM TEMP STORAGE WHEN OPENED
(≤ 86°F [30°C])

Admelog SoloStar pen Insulin lispro 28 days Do not refrigerate

Admelog vial Insulin lispro 28 days Room or Refrigerated (≤ 86°F [30°C])

Apidra SoloStar pen Insulin glulisine 28 days (≤ 77°F [25°C]) ≤ 77°F (25°C), but do not refrigerate

Apidra vial Insulin glulisine 28 days (≤ 77°F [25°C]) Room or Refrigerated (≤ 77°F [25°C])

Basaglar KwikPen Insulin glargine 28 days Do not refrigerate

Fiasp FlexTouch pen Insulin aspart 28 days Room or Refrigerated (≤ 86°F [30°C])

Fiasp PenFill cartridge Insulin aspart 28 days Do not refrigerate

Fiasp vial Insulin aspart 28 days Room or Refrigerated (≤ 86°F [30°C])

Humalog KwikPen Insulin lispro 28 days Do not refrigerate

Humalog vial Insulin lispro 28 days Room or Refrigerated (≤ 86°F [30°C])

Humalog Junior KwikPen Insulin lispro 28 days Do not refrigerate

Humalog TempoPen Insulin lispro 28 days Do not refrigerate

Humalog Mix 50/50 KwikPen Insulin lispro protamine/lispro 10 days Do not refrigerate

Humalog Mix 50/50 vial Insulin lispro protamine/lispro 28 days Do not refrigerate

Humalog Mix 75/25 KwikPen Insulin lispro protamine/lispro 10 days Do not refrigerate

Humalog Mix 75/25 vial Insulin lispro protamine/lispro 28 days Room or Refrigerated (≤ 86°F [30°C])

Humulin N KwikPen NPH 14 days Do not refrigerate

Humulin N vial NPH 31 days Room or Refrigerated (≤ 86°F [30°C])

Humulin R vial Regular 31 days Room or Refrigerated (≤ 86°F [30°C])

Humulin R U-500 KwikPen Regular 28 days Do not refrigerate

Humulin R U-500 vial Regular 40 days Room or Refrigerated (≤ 86°F [30°C])

Humulin 70/30 KwikPen NPH/regular 10 days Do not refrigerate

Humulin 70/30 vial NPH/regular 31 days Room or Refrigerated (≤ 86°F [30°C])

Lantus SoloStar pen Insulin glargine 28 days Do not refrigerate

Lantus vial Insulin glargine 28 days Room or Refrigerated (≤ 86°F [30°C])

Levemir FlexPen Insulin detemir 42 days Do not refrigerate

Levemir vial Insulin detemir 42 days Room or Refrigerated (≤ 86°F [30°C])

Lyumjev pen Insulin lispro-aabc 28 days Do not refrigerate

Lyumjev vial Insulin lispro-aabc 28 days Room or Refrigerated (≤ 86°F [30°C])

Continued on next page ⟶

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 Reference(s): 6-24

Insulin Storage Requirements (cont.)

All products are good until their expiration date when kept unopened and
refrigerated (36°F-46°F [2°C-8°C]).

DAYS GOOD AT
BRAND GENERIC ROOM TEMP STORAGE WHEN OPENED
(≤ 86°F [30°C])

Novolin N FlexPen NPH 28 days Do not refrigerate

Novolin N vial NPH 42 days (≤ 77°F [25°C]) ≤ 77°F (25°C), but do not refrigerate

Novolin R FlexPen Regular 28 days Do not refrigerate

Novolin R vial Regular 42 days (≤ 77°F [25°C]) ≤ 77°F (25°C), but do not refrigerate

Novolin 70/30 FlexPen NPH/regular 28 days Do not refrigerate

Novolin 70/30 vial NPH/regular 42 days (≤ 77°F [25°C]) ≤ 77°F (25°C), but do not refrigerate

NovoLog FlexTouch/FlexPen Insulin aspart 28 days Do not refrigerate

NovoLog vial Insulin aspart 28 days Room or Refrigerated (≤ 86°F [30°C])

NovoLog PenFill cartridge Insulin aspart 28 days Do not refrigerate

NovoLog Mix 70/30 FlexPen Insulin aspart 14 days Do not refrigerate

NovoLog Mix 70/30 vial Insulin aspart 28 days Room or Refrigerated (≤ 86°F [30°C])

Rezvoglar KwikPen Insulin glargine-aglr 28 days Do not refrigerate

Semglee pen Insulin glargine-yfgn 28 days Do not refrigerate

Semglee vial Insulin glargine-yfgn 28 days Room or Refrigerated (≤ 86°F [30°C])

Toujeo SoloStar pen Insulin glargine 56 days Do not refrigerate

Toujeo Max SoloStar pen Insulin glargine 56 days Do not refrigerate

Tresiba FlexTouch pen Insulin degludec 56 days Room or Refrigerated (≤ 86°F [30°C])

Tresiba vial Insulin degludec 56 days Room or Refrigerated (≤ 86°F [30°C])

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 Reference(s): 27-32, 51, 60-62

Injection Areas
Insulin Injection Areas

Insulin is best absorbed when injected into the abdomen (staying away from the
belly button by about 2 fingers width or a few inches); however, the outer thighs,
upper buttocks and backs of arms are also acceptable injection areas.

Using the same injection area (e.g., abdomen) for each administration can help
ensure the body receives consistent levels of insulin.

Rotate injection sites (in the same general body region) to prevent skin damage.

If using a GLP-1 RA or GLP-1/GIP RA with insulin, administer at separate injection

sites and do not mix the medications. The injection sites may be in the same body
region but should not be adjacent to each other.

GLP-1 RA and GLP-1/GIP RA Injection Areas

GLP-1 RAs and GLP-1/GIP RAs (e.g., tirzepatide) can be injected into the abdomen
(staying away from the belly button by about 2 fingers width or a few inches),
outer thighs and backs of arms.

Rotate injection sites (in the same general body region) to prevent skin damage.

If using a GLP-1 RA or GLP-1/GIP RA with insulin, administer at separate injection

sites and do not mix the medications. The injection sites may be in the same body
region but should not be adjacent to each other.

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17
Diabetes Drugs: Cardiovascular and Renal Effects Reference(s): 1, 6-51, 58-59

DRUG/CLASS ASCVD EFFECT HF EFFECT RENAL EFFECT RENAL DOSING/USE*

Metformin Potential benefit Neutral Neutral Contraindicated with

Oral eGFR < 30 mL/min

SGLT2is† FDA approved for CVD benefit: FDA approved for HF benefit: FDA approved: Renal dose adjustments
Oral • canagliflozin • dapagliflozin • canagliflozin (DKD benefit) necessary

• empagliflozin • empagliflozin • dapagliflozin (CKD benefit)

• empagliflozin (CKD benefit)
Neutral: Evidence for benefit:
• bexagliflozin** • canagliflozin Neutral:
• dapagliflozin • ertugliflozin • bexagliflozin**
• ertugliflozin • ertugliflozin

GLP-1 RAs§ FDA approved for CVD benefit: Neutral Evidence for benefit: Renal dose adjustments
SUBQ injection • dulaglutide • dulaglutide necessary for exenatide and
(except oral lixisenatide
semaglutide) • liraglutide • liraglutide
• semaglutide (SUBQ) • semaglutide (SUBQ) Not necessary for dulaglutide,
liraglutide, or semaglutide (oral
Neutral: and SUBQ); however, monitoring
for adverse effects is warranted
• exenatide ER
• lixisenatide
• semaglutide (oral)

* Review individual manufacturer’s product labeling for specific renal dosing adjustments and considerations
** Bexagliflozin was FDA-approved in 2023 and has limited data suggesting neutral cardiorenal effect
† Sotagliflozin (SGLT1/2i) is a recommended option to provide heart failure benefit in patients with T2DM and heart failure (it is not approved for glycemic control)
§ Tirzepatide (GLP-1/GIP RA) is currently under investigation for cardiovascular and renal benefit

ALGrawany
18
Diabetes Drugs: Cardiovascular and Renal Effects (cont.) Reference(s): 1, 6-51

DRUG/CLASS ASCVD EFFECT HF EFFECT RENAL EFFECT RENAL DOSING/USE*

DPP-4is Neutral Potential risk Neutral Renal dose adjustments necessary for
Oral • saxagliptin alogliptin, saxagliptin and sitagliptin

Not necessary for linagliptin

TZDs Potential CVD benefit: Increased risk: Neutral Renal dose adjustments not necessary
Oral • pioglitazone • FDA boxed warning for - - -
- - - -congestive heart failure Generally not recommended in renal impairment
due to the potential for fluid retention

Sulfonylureas Neutral Neutral Neutral Glyburide:

(2nd generation) Generally not recommended in renal impairment
Oral
Glimepiride, glipizide:
Use lower initial dosing and titrate carefully

Insulin Analogs Neutral Neutral Neutral Caution:

SUBQ injection Lower insulin doses necessary with
decreased renal function
Human Insulin
SUBQ injection, Titrate according to clinical response
inhaled

* Review individual manufacturer’s product labeling for specific renal dosing adjustments and considerations

19
Metformin: Dosing and Indications Reference(s): 1, 25-26, 57

Metformin typically reduces A1C by 1.5-2.0% and may promote mild weight reduction.

DRUG INDICATIONS DOSING RENAL DOSING HEPATIC DOSING

Metformin IR Improved glycemic Initial Dosing: eGFR 30-45 mL/min: Use not recommended in
(Glucophage) control in T2DM 500 mg PO BID with meals, OR hepatic impairment due to
• Initiation not recommended
850 mg PO once daily with meals concerns for lactic acidosis
• Reassess risk-benefit of - - -
Max Dosing: - - - continued therapy
2550 mg PO daily
(in divided doses given with meals) eGFR < 30 mL/min:
• Use is contraindicated
Titration:
Increase dose by 500 mg weekly or • Discontinue therapy if
850 mg every 2 weeks as tolerated eGFR falls below 30 mL/min
for added glycemic control

Doses > 2000 mg daily may be given in Hemodialysis:

three divided doses for improved tolerance • Use is contraindicated

Metformin ER Improved glycemic Initial Dosing: eGFR 30-45 mL/min: Use not recommended in
(Glucophage XR) control in T2DM 500 mg ER PO once daily hepatic impairment due to
• Initiation not recommended
with evening meal concerns for lactic acidosis
• Reassess risk-benefit of - - -
Max Dosing: - - - continued therapy
2000 mg ER daily
(with evening meal or in divided doses with meals) eGFR < 30 mL/min:
• Use is contraindicated
Titration:
Increase dose by 500 mg increments • Discontinue therapy if eGFR
every week as tolerated for added - - - falls below 30 mL/min
glycemic control
Hemodialysis:
If glycemic control is not achieved
with 2000 mg ER once daily, • Use is contraindicated
consider 1000 mg ER twice daily (with meals)

20
GLP-1 RAs and GLP-1/GIP RA: Efficacy and Safety Reference(s): 1, 28-34, 57

GLP-1 receptor agonists typically reduce A1C by 0.7-2.1% and can reduce body weight by 1.4-5.5 kg, depending on the individual agent and dosing utilized.
Tirzepatide (GLP-1/GIP RA) typically reduces A1C by 1.7-2.3% and can reduce body weight by 6.3-11.2 kg, depending on the dosing utilized.

RELATIVE RELATIVE RELATIVE

DRUG CARDIORENAL EFFECTS
A1C LOWERING* WEIGHT LOWERING* GI SIDE EFFECTS

Dulaglutide FDA approved for CVD benefit

Trulicity
●●●● ●●● ●●●
SUBQ injection Evidence for renal benefit

Exenatide No data
Byetta
●● ●● ●
SUBQ injection

Exenatide ER Neutral CVD effect

Bydureon, Bydureon BCise ●● ●● ●
SUBQ injection

Liraglutide^ FDA approved for CVD benefit

Victoza
●● ●●● ●●
SUBQ injection Evidence for renal benefit

Lixisenatide Neutral CVD effect

Adlyxin
●● ●● ●●●
SUBQ injection

Semaglutide^ FDA approved for CVD benefit

Ozempic
●●●● ●●●● ●●●
SUBQ injection Evidence for renal benefit

Semaglutide Neutral CVD effect

Rybelsus
●●● ●●● ●●
Oral tablet

Tirzepatide** Under investigation for CVD and renal benefit

Mounjaro
●●●●● ●●●●● ●●
SUBQ injection

* The relative efficacies for A1C lowering and weight loss are based upon data from clinical trials included in the manufacturer's product labeling, post-marketing studies, and guidance from the American Diabetes Association: Standards of Care. The relative GI side effect profiles listed and ranked above are based upon
information included in the manufacturer’s product labeling. Actual patient A1C reduction, weight loss and side effect profile may differ in practice based upon baseline patient characteristics, concomitant pharmacotherapy, or other factors.
** Tirzepatide is a dual GLP-1/GIP receptor agonist (all other drugs listed in the chart above are GLP-1 RA only).
^ Note that Saxenda (liraglutide), Wegovy (semaglutide) and Zepbound (tirzepatide) are approved for weight-loss in patients with/without type 2 diabetes at higher than conventional dosing for glycemic control. These specific products are intentionally excluded from this chart as they fall outside the scope of the comparison.

ALGrawany
21
GLP-1 RAs and GLP-1/GIP RA: Dosing and Indications Reference(s): 1, 28-34

DRUG INDICATIONS DOSING RENAL DOSING HEPATIC DOSING

Dulaglutide Improved glycemic Initial Dosing: No dose adjustment No dose adjustment

Trulicity control in T2DM 0.75 mg once weekly necessary necessary

SUBQ injection Cardiovascular Max Dosing:

risk reduction 4.5 mg once weekly
(in patients with T2DM
plus established CVD Titration:
or multiple risk factors)
• Increase to 1.5 mg/week for added glycemic control
• If additional glycemic control is needed, increase the dosage in
- 1.5 mg increments after at least 4 weeks on the current dosage

Exenatide Improved glycemic Initial Dosing: CrCl < 30 mL/min: Unknown,

Byetta control in T2DM 5 mcg BID (within 60 minutes of meals) but not expected
Use not recommended
to require dose
SUBQ injection Max Dosing: adjustments
10 mcg BID Dialysis: (primarily excreted renally)
Use not recommended
Titration:
After 1 month of therapy,
may increase to 10 mcg BID for added glycemic control

Exenatide ER Improved glycemic Initial Dosing: eGFR < 45 mL/min: Unknown,

Bydureon, control in T2DM 2 mg ER once weekly but not expected
Use not recommended
Bydureon BCise to require dose
Max Dosing: adjustments
SUBQ injection 2 mg ER once weekly Dialysis: (primarily excreted renally)
Use not recommended

The combined use of GLP-1 RAs, tirzepatide (GLP-1/GIP RA) and/or DPP-4 inhibitors is not recommended due to their similar mechanism of action.

22
GLP-1 RAs and GLP-1/GIP RA: Dosing and Indications (cont.) Reference(s): 1, 28-34

DRUG INDICATIONS DOSING RENAL DOSING HEPATIC DOSING

Liraglutide Improved glycemic Initial Dosing: No dose adjustment No dose adjustment

Victoza control in T2DM 0.6 mg once daily for 1 week necessary necessary
Note - the 0.6 mg dose is not effective for glycemic control
SUBQ injection Cardiovascular
and is being used to limit GI symptoms during the initial titration
risk reduction
(in patients with T2DM Max Dosing:
plus established CVD)
1.8 mg daily
Note:
Saxenda is a higher dose Titration:
liraglutide product • After 1 week of 0.6 mg daily, increase to 1.2 mg daily
approved for weight loss • If additional glycemic control is required, increase to 1.8 mg daily -
(not included here) - after at least one week of treatment with 1.2 mg daily

Lixisenatide Improved glycemic Initial Dosing: eGFR 15-30 mL/min: Unknown, but not
Adlyxin control in T2DM 10 mcg once daily for 14 days • Use with caution expected to require
dose adjustments
SUBQ injection Max Dosing: eGFR < 15 mL/min:
20 mcg daily • Use not recommended
Titration:
After 14 days, increase to 20 mcg once daily

Semaglutide Improved glycemic Initial Dosing: No dose adjustment No dose adjustment

Ozempic control in T2DM 0.25 mg once weekly for 4 weeks necessary necessary

SUBQ injection Note - the 0.25 mg dose is not intended for glycemic control
Cardiovascular and is being used to limit GI symptoms during the initial titration
risk reduction
(in patients with T2DM Max Dosing:
and established CVD) 2 mg once weekly
Note: Titration:
Wegovy is a higher dose • After 4 weeks of 0.25 mg weekly, increase to 0.5 mg weekly
semaglutide product
approved for weight loss • If additional glycemic control is needed after at least 4 weeks of - -
(not included here) - 0.5 mg weekly, the dosage may be increased to 1 mg weekly
• If additional glycemic control is needed after at least 4 weeks of - -
- 1 mg weekly, the dosage may be increased to 2 mg weekly

The combined use of GLP-1 RAs, tirzepatide (GLP-1/GIP RA) and/or DPP-4 inhibitors is not recommended due to their similar mechanism of action.

23
GLP-1 RAs and GLP-1/GIP RA: Dosing and Indications (cont.) Reference(s): 1, 28-34

DRUG INDICATIONS DOSING RENAL DOSING HEPATIC DOSING

Semaglutide Improved glycemic Initial Dosing: No dose adjustment No dose adjustment

Rybelsus control in T2DM 3 mg PO once daily for 30 days necessary necessary

Oral tablet Note - the 3 mg dose is not effective for glycemic control
and is being used to limit GI symptoms during the initial titration

Max Dosing:
14 mg daily

Titration:
• After 30 days of 3 mg daily, increase to 7 mg daily
• If additional glycemic control is needed after at least 30 days on - -
- the 7 mg dose, the dosage may be increased to 14 mg daily

Special Dosing Instructions:

Take each dose at least 30 minutes prior to first food, beverage or
oral medication(s) with no more than 4 oz of plain water

Tirzepatide Improved glycemic Initial Dosing: No dose adjustment No dose adjustment

Mounjaro control in T2DM 2.5 mg once weekly for 4 weeks necessary necessary

GLP-1/GIP RA Note - the 2.5 mg dose is not intended for glycemic control
and is being used to limit GI symptoms during the initial titration
SUBQ injection
Max Dosing:
15 mg once weekly

Titration:
• After 4 weeks of 2.5 mg weekly, increase to 5 mg weekly
• If additional glycemic control is needed, increase the dosage in - -
- 2.5 mg increments after at least 4 weeks on the current dose

The combined use of GLP-1 RAs, tirzepatide (GLP-1/GIP RA) and/or DPP-4 inhibitors is not recommended due to their similar mechanism of action.

24
SGLT2 Inhibitors: Efficacy and Safety Reference(s): 3-5, 40-44, 61-63

SGLT2 inhibitors typically reduce A1C by 0.5-1.0% and can reduce body weight by ~3 kg.

RELATIVE RELATIVE
DRUG † CARDIORENAL EFFECTS SAFETY CONCERNS
A1C LOWERING* WEIGHT LOWERING*

Bexagliflozin Limited data suggests • Increased urinary frequency

Brenzavvy
●● neutral effect;
●●
however, additional trials are needed • Volume depletion

• Urinary tract infections

Canagliflozin FDA approved for CVD benefit
Invokana
●● ●●
• Genital mycotic infections
FDA approved for DKD benefit
• Fournier’s gangrene
Evidence for HF benefit

Dapagliflozin FDA approved for HF benefit

Farxiga
●● ●●
FDA approved for CKD benefit

Neutral CVD effect

Empagliflozin FDA approved for CVD benefit

Jardiance
●● ●●
FDA approved for HF benefit

FDA approved for CKD benefit

Ertugliflozin Neutral CVD effect

Steglatro
●● ●●
Neutral renal effect

Evidence for HF benefit

* These relative efficacy points are based on clinical trial data involving monotherapy and combination therapy in patients with type 2 diabetes. Actual patient A1C reduction and weight loss in practice may differ based upon baseline patient characteristics, concomitant pharmacotherapy, or other factors.
† Sotagliflozin (SGLT1/2i) is a recommended option to provide heart failure benefit in patients with T2DM and heart failure (it is not approved for glycemic control). For this reason it is not included in this table.

25
SGLT2 Inhibitors: Dosing and Indications
DRUG INDICATIONS
Bexagliflozin T2DM: improved glycemic control
Brenzavvy
Canagliflozin T2DM: improved glycemic control
Invokana
Cardiovascular risk reduction
(in patients with T2DM & established CVD)
Renal risk reduction
(in patients with T2DM & diabetic
nephropathy)
Dapagliflozin T2DM: improved glycemic control
Farxiga
Heart failure risk reduction
(in patients with or without T2DM)
Renal risk reduction
(in patients with CKD with or without T2DM)
Empagliflozin T2DM: improved glycemic control
Jardiance Cardiovascular risk reduction
(in patients with T2DM & established CVD)
Heart failure risk reduction
(in patients with or without T2DM)
Renal risk reduction
(in patients with CKD with or without T2DM)
Ertugliflozin T2DM: improved glycemic control
Steglatro
Sotagliflozin CV and HF risk reduction
Inpefa (in patients with HF or patients with
T2DM, CKD and CV risk factors)
Reference(s): 35-40
DOSING RENAL DOSING HEPATIC DOSING
Initial Dosing: 20 mg PO once daily in the morning eGFR < 30 mL/min: Mild to moderate impairment:
• Not recommended No dose adjustment necessary
Max Dosing: 20 mg daily
Dialysis: Use is contraindicated Severe impairment:
Not studied, not recommended
Initial Dosing: eGFR < 60 mL/min: Limit to 100 mg daily Mild to moderate
100 mg PO once daily (take before 1st meal of the day) impairment:
eGFR < 30 mL/min:
No dose adjustment necessary
Max Dosing: 300 mg daily • Initiation not recommended
• Not recommended for glycemic control Severe impairment:
Titration: Not studied, not recommended
• May continue at 100 mg daily for renal risk reduction
May increase to 300 mg daily for added glycemic control .
Dialysis: Use is contraindicated
Initial Dosing: eGFR < 45 mL/min: Not recommended for glycemic control No dose adjustment necessary
• 5 mg PO once daily (for glycemic control)
eGFR < 25 mL/min:
• 10 mg PO once daily (for heart failure or renal risk reduction) However, use in severe
• Initiation not recommended impairment has not been
Max Dosing: 10 mg daily
• Use for other indications (e.g., heart failure, chronic - - - - studied (use with caution)
Titration: - kidney disease) may continue at 10 mg daily
May increase to 10 mg daily for added glycemic control .
(no titration for heart failure or renal risk reduction indications) Dialysis: Use is contraindicated
Initial Dosing: 10 mg PO once daily in the morning eGFR < 30 mL/min: No dose adjustment necessary
• Not recommended for glycemic control
Max Dosing: 25 mg daily
• Insufficient data to specify dosing for CV risk reduction
Titration: eGFR < 20 mL/min:
May increase to 25 mg daily for added glycemic control
• Insufficient data to specify dosing for HF/CKD risk reduction
Dialysis: Use is contraindicated
Initial Dosing: 5 mg PO once daily in the morning eGFR < 45 mL/min: Use not recommended Mild to moderate impairment:
No dose adjustment necessary
Max Dosing: 15 mg daily
Dialysis: Use is contraindicated
Titration: Severe impairment:
May increase to 15 mg daily for added glycemic control Not studied, not recommended
Initial Dosing: 200 mg PO once daily not more than 1 hour Dose adjustments not specified (use with caution) Mild impairment:
before 1st meal of the day No dose adjustment necessary
Max Dosing: 400 mg daily Moderate to severe impairment:
Titration: Not studied, not recommended
Up-titrate after at least 2 weeks to 400 mg, as tolerated
ALGrawany
26
DPP-4 Inhibitors: Efficacy and Safety Reference(s): 1, 41-44, 57

DPP-4 inhibitors typically reduce A1C by 0.5-0.9% and are weight neutral.

RELATIVE RELATIVE
DRUG CARDIORENAL EFFECTS SAFETY CONCERNS
A1C LOWERING* WEIGHT LOWERING*

Alogliptin Neutral cardiovascular effect Neutral effect • Pancreatitis

Nesina
●
Neutral renal effect • Heart failure

Evidence for heart failure risk: • Arthralgia

Linagliptin • saxagliptin
Tradjenta
●

Saxagliptin
Onglyza
●

Sitagliptin
Januvia
●

* These relative efficacy points are based on clinical trial data involving monotherapy and combination therapy in patients with type 2 diabetes. Actual patient A1C reduction and weight loss in practice may differ based upon baseline patient characteristics, concomitant pharmacotherapy, or other factors.

27
DPP-4 Inhibitors: Dosing and Indications Reference(s): 41-44

DRUG INDICATIONS DOSING RENAL DOSING HEPATIC DOSING

Alogliptin Improved glycemic Initial Dosing: CrCl 30 to < 60 mL/min: 12.5 mg once daily Mild to moderate impairment:
Nesina control in T2DM 25 mg PO once daily No dose adjustment necessary
(dosed renally) CrCl < 30 mL/min: 6.25 mg once daily
Severe impairment:
Max Dosing: Hemodialysis: 6.25 mg once daily Insufficient data
6.25 mg to 25 mg daily (administer without regard to
(dependent on renal function) timing of hemodialysis) Pharmacokinetics Pearl:
Alogliptin is not extensively metabolized
and drug levels are not expected to be
meaningfully impacted (use with caution)

Linagliptin Improved glycemic Initial Dosing: No dose adjustment necessary No dose adjustment necessary
Tradjenta control in T2DM 5 mg PO once daily

Max Dosing:
5 mg daily

Saxagliptin Improved glycemic Initial Dosing: eGFR < 45 mL/min: 2.5 mg once daily No dose adjustment necessary
Onglyza control in T2DM 2.5 mg to 5 mg PO once daily
(dosed renally) Hemodialysis: 2.5 mg once daily
(administer after hemodialysis)
Max Dosing:
2.5 mg to 5 mg daily
(dependent on renal function)

Sitagliptin Improved glycemic Initial Dosing: eGFR 30 mL/min to <45 mL/min: Mild to moderate impairment:
Januvia control in T2DM 100 mg PO once daily 50 mg once daily No dose adjustment necessary
(dosed renally)
eGFR < 30 mL/min: 25 mg once daily Severe impairment:
Max Dosing: Insufficient data
25 mg to 100 mg daily Dialysis: 25 mg once daily
(dependent on renal function) (administer without regard to Pharmacokinetics Pearl:
Sitagliptin is not extensively metabolized
timing of dialysis) and drug levels are not expected to be
meaningfully impacted (use with caution)

The combined use of GLP-1 RAs, tirzepatide (GLP-1/GIP RA) and/or DPP-4 inhibitors is not recommended due to their similar mechanism of action.

28
Sulfonylureas: Efficacy and Safety Reference(s): 1, 45-49, 57, 60

Sulfonylureas typically reduce A1C by 1.5-2.0% and can cause weight gain of ~1-2 kg.

RELATIVE RELATIVE RELATIVE

DRUG CARDIORENAL EFFECTS
A1C LOWERING* HYPOGLYCEMIA RISK* WEIGHT GAIN*

Glipizide Neutral cardiovascular effect Immediate-release:

Glucotrol,
●●● ●●
Glucotrol XL Neutral renal effect:
●●
Use caution with renal impairment due to
Glipizide is a short-acting sulfonylurea
increased risk for hypoglycemia
and is currently listed on the Beers Criteria as
(particularly with the ER tablet)
a preferred option to long-acting sulfonylureas
(use with extreme caution in elderly patients)

Extended-release:
●●●

Glimepiride Neutral cardiovascular effect

Amaryl
●●● ●●● ●●
Neutral renal effect: Glimepiride is a long-acting sulfonylurea
Use caution with renal impairment due to and is currently listed on the Beers Criteria
increased risk for hypoglycemia (use with extreme caution in elderly patients)

Glyburide Neutral cardiovascular effect

Diabeta,
●●● ●●●● ●●
Glynase PresTab, Neutral renal effect: Glyburide is a long-acting sulfonylurea with
Micronase Generally not recommended with renally excreted active metabolites and is
renal impairment due to increased risk for currently listed on the Beers Criteria
hypoglycemia (use with extreme caution in elderly patients)

* These relative efficacy and risk points are based on clinical trial data involving monotherapy and combination therapy in patients with type 2 diabetes. Actual patient A1C reduction and weight gain in practice may differ based upon baseline patient characteristics, concomitant pharmacotherapy, or other factors.

29
Sulfonylureas: Dosing and Indications
DRUG INDICATIONS DOSING
Improved glycemic Initial Dosing: 5 mg PO once daily
Glipizide
control in T2DM 30 minutes prior to breakfast
Glucotrol
Consider lower initial dose (2.5 mg daily)
in patients at increased risk for hypoglycemia
Max Dosing: 40 mg daily
(daily doses > 15 mg should be divided)
Titration:
May adjust dose in 2.5-5 mg
increments for added glycemic control
(no more frequently than every several days)
Improved glycemic Initial Dosing: 5 mg ER PO once daily
Glipizide ER
control in T2DM with breakfast (or first main meal)
Glucotrol XL
Consider lower initial dose (2.5 mg ER daily)
in patients at increased risk for hypoglycemia
Max Dosing: 20 mg ER daily
Titration:
Dose adjustments can be made
according to glycemic control
Improved glycemic Initial Dosing: 1-2 mg PO once daily
Glimepiride
control in T2DM with breakfast (or first main meal)
Amaryl
Consider lower initial dose (1 mg daily)
in patients at increased risk for hypoglycemia
Max Dosing: 8 mg daily
Titration:
May adjust dose in 1-2 mg increments
for added glycemic control
(no more frequently than every 1-2 weeks)
Reference(s): 45-49
RENAL DOSING HEPATIC DOSING
Use lower initial dosing and titrate carefully Use lower initial dosing and titrate carefully
Pharmacokinetics Pearl:
Pharmacokinetics Pearl: As glipizide is heavily protein bound and metabolism is primarily
Given that excretion is primarily via the renal route it is likely that renal
hepatic it is likely that hepatic dysfunction will increase the duration
dysfunction will increase duration and effect of drug (use with caution)
and effect of this agent (use with caution)
Dialysis:
Dose adjustments not specified in prescribing information
Pharmacokinetics Pearl:
Glipizide is heavily protein bound and likely not significantly affected
by dialysis (use not recommended)
Use lower initial dosing and titrate carefully Use lower initial dosing and titrate carefully
Pharmacokinetics Pearl:
Pharmacokinetics Pearl: As glipizide is heavily protein bound and metabolism is primarily
Given that excretion is primarily via the renal route it is likely that renal hepatic it is likely that hepatic dysfunction will increase the duration
dysfunction will increase duration and effect of drug (use with caution) and effect of this agent (use with caution)
Dialysis:
Dose adjustments not specified in prescribing information
Pharmacokinetics Pearl:
Glipizide is heavily protein bound and likely not significantly affected
by dialysis (use not recommended)
Use lower initial dose (1 mg) in patients with Dose adjustments not specified in prescribing information
renal impairment and titrate carefully due to lack of adequate studies
Pharmacokinetics Pearl:
Pharmacokinetics Pearl: As glimepiride is heavily protein bound and metabolism is primarily
Given that excretion is primarily via the renal route it is likely that renal hepatic it is likely that hepatic dysfunction will increase the duration
dysfunction will increase duration and effect of drug (use with caution) and effect of this agent (use with caution)
Dialysis:
Dose adjustments not specified in prescribing information
Pharmacokinetics Pearl:
Glimepiride is heavily protein bound and likely not significantly
affected by dialysis (use not recommended)
30
Sulfonylureas: Dosing and Indications (cont.) Reference(s): 45-49, 56

DRUG INDICATIONS DOSING RENAL DOSING HEPATIC DOSING

Improved glycemic Initial Dosing: Use lower initial dose (1.25 mg) in patients with Use lower initial dose (1.25 mg) in patients with
Glyburide
control in T2DM 2.5 mg to 5 mg PO once daily renal impairment and titrate carefully hepatic impairment (titrate cautiously)
Diabeta,
with breakfast (or first main meal)
Micronase Pharmacokinetics Pearl:
Pharmacokinetics Pearl: As glyburide is heavily protein bound and metabolism is primarily
Consider lower initial dose (1.25 mg daily) Given that excretion is primarily via the renal route it is likely that renal hepatic it is likely that hepatic dysfunction will increase the duration
in patients at increased risk for hypoglycemia dysfunction will increase duration and effect of drug (use with caution) and effect of this agent (use with caution)

Max Dosing: 20 mg daily

(single or divided dosing) Dialysis:
Dose adjustments not specified in prescribing information
Consider BID dosing when daily dose > 10 mg

Pharmacokinetics Pearl:
Titration: Glyburide is heavily protein bound and likely not significantly affected
Dosage increases should be made in by dialysis (use not recommended)
increments of no more than 2.5 mg
at weekly intervals according
to glycemic control

Improved glycemic Initial Dosing: Use lower initial dose (0.75 mg) in patients with Use lower initial dose (0.75 mg) in patients with
Glyburide,
control in T2DM 1.5 mg to 3 mg PO once daily renal impairment and titrate carefully hepatic impairment (titrate cautiously)
micronized with breakfast (or first main meal)
Glynase PresTab Pharmacokinetics Pearl:
Pharmacokinetics Pearl:
As glyburide is heavily protein bound and metabolism is primarily
Consider lower initial dose (0.75 mg daily) Given that excretion is primarily via the renal route it is likely that renal hepatic it is likely that hepatic dysfunction will increase the duration
PresTabs are not in patients at increased risk for hypoglycemia dysfunction will increase duration and effect of drug (use with caution) and effect of this agent (use with caution)
bioequivalent to
glyburide tablets Max Dosing: 12 mg daily
(single or divided dosing) Dialysis:
Dose adjustments not specified in prescribing information
Consider BID dosing when daily dose > 6 mg

Pharmacokinetics Pearl:
Titration: Glyburide is heavily protein bound and likely not significantly affected
Dosage increases should be made in by dialysis (use not recommended)
increments of no more than 1.5 mg
at weekly intervals according
to glycemic control

31
Thiazolidinediones: Efficacy and Safety Reference(s): 1, 50-51, 57

Thiazolidinediones typically reduce A1C by 1.0-1.5% and can cause weight gain of ~4 kg.

RELATIVE RELATIVE
DRUG CARDIORENAL EFFECTS OTHER CONSIDERATIONS
A1C LOWERING* WEIGHT GAIN*

Congestive heart failure risk

Pioglitazone
●●● Increased heart failure risk ●●●
Actos Risk for bladder cancer
Potential cardiovascular benefit
Risk for fluid retention
Neutral renal effect: Risk for bone fracture
Generally not recommended with renal impairment
due to increased risk for fluid retention

Congestive heart failure risk

Rosiglitazone
●●● Increased heart failure risk ●●●
Avandia Increased LDL levels
Neutral cardiovascular effect
Risk for fluid retention
Neutral renal effect: Risk for bone fracture
Generally not recommended with renal impairment
due to increased risk for fluid retention Brand only ($$$)

* These relative efficacy and risk points are based on clinical trial data involving monotherapy and combination therapy in patients with type 2 diabetes. Actual patient A1C reduction and weight gain in practice may differ based upon baseline patient characteristics, concomitant pharmacotherapy, or other factors.

Thiazolidinediones: Dosing and Indications

DRUG INDICATIONS DOSING RENAL DOSING HEPATIC DOSING

Pioglitazone Improved glycemic Initial Dosing: 15 mg to 30 mg PO once daily No dose adjustment No dose adjustment
Actos control in T2DM A lower initial dose of 15 mg recommended in patients with congestive HF (NYHA class I or II) necessary necessary
Max Dosing: 45 mg daily Generally not recommended
with renal impairment
due to increased risk for
Titration: fluid retention
May increase dose in 15 mg increments according to glycemic control

Rosiglitazone Improved glycemic Initial Dosing: 4 mg PO daily (as single or two divided doses) No dose adjustment Dose adjustments not specified in
Avandia prescribing information:
control in T2DM necessary
Max Dosing: 8 mg daily However, rosiglitazone should not
Generally not recommended
be used in patients with evidence of
Titration: with renal impairment
active liver disease or ALT levels
due to increased risk for
After 8-12 weeks, the dose may be increased to 8 mg daily > 2.5 times the upper limit of normal
fluid retention
for added glycemic control

32
 Reference(s): 53

Drugs that Cause Hyperglycemia

CATEGORY EXAMPLES

Atypical antipsychotics Most risk

Clozapine, olanzapine

Intermediate risk
Iloperidone, paliperidone, quetiapine, risperidone

Least risk
Aripiprazole, ziprasidone

Beta-blockers*^ Atenolol, metoprolol, propranolol

Systemic corticosteroids Methylprednisolone, prednisone, prednisolone

Immunosuppressants Cyclosporine, sirolimus, tacrolimus

Atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir,

Protease inhibitors
ritonavir, saquinavir, tipranavir

Ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin,

Quinolones*
norfloxacin, ofloxacin

Chlorothiazide, chlorthalidone, hydrochlorothiazide,

Thiazide-type diuretics
indapamide, metolazone

*Also known to cause hypoglycemia

^Carvedilol and nebivolol are not associated with hyperglycemia

33
 Reference(s): 54-55

Drugs that Cause Hypoglycemia

CATEGORY EXAMPLES

ACE inhibitors Benazepril, enalapril, lisinopril, ramipril, quinapril, etc.

Alcohol Alcoholic beverages

Antiarrhythmics Cibenzoline, disopyramide, quinidine

Ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin,

Quinolone antibiotics*
norfloxacin, ofloxacin

Antibiotics (misc.) Chloramphenicol, chloroquine, linezolid, pentamidine

All drugs for type 2 diabetes work to lower blood sugars;

Antidiabetics there is notable hypoglycemia risk with insulins, sulfonylureas,
thiazolidinediones, and when combining multiple agents

Beta-blockers* Nadolol, propranolol, sotalol, timolol

Anti-obesity drug Lorcaserin

Salicylates Aspirin, magnesium salicylate, salsalate

*Also known to cause hyperglycemia

34
 Reference(s): 1

Hypoglycemia Classification & Treatment

Symptoms of hypoglycemia include, but are not limited to:
• Hunger • Irritability • Shakiness • Tachycardia

If allowed to progress hypoglycemia can lead to loss of consciousness. In severe cases,

hypoglycemia may lead to seizure, coma and death.

All patients should be screened for their risk of hypoglycemia as well as for any impaired
awareness of hypoglycemia. A patient’s history of hypoglycemia should be reviewed and evaluated
during each and every clinical encounter.

Those with reduced hypoglycemia awareness should be referred to a trained healthcare

professional in order to re-establish awareness of the appropriate signs and symptoms of
hypoglycemia. If impaired or declining cognitive function is suspected/found, routine assessment
with an added emphasis on identifying and preventing hypoglycemia is warranted.

If a patient experiences a Level 2 hypoglycemic event without any reported symptoms it is likely
they have impaired hypoglycemia awareness.

Careful consideration of a patient’s risk for hypoglycemia is warranted when selecting or adjusting
glycemic goals and glucose-lowering therapy.

Continuous glucose monitoring (CGM) devices have been shown to be effective in reducing the
incidence of hypoglycemia and are useful for revealing asymptomatic episodes in patients receiving
insulin therapy. CGMs are recommended for those at a high-risk for hypoglycemia.

Classification of Hypoglycemia

CATEGORY GLYCEMIC CRITERIA/DESCRIPTION

Level 1 Glucose <70 mg/dL and ≥54 mg/dL

Level 2 Glucose <54 mg/dL

Severe event characterized by altered mental status and/or

Level 3 physical status requiring assistance for treatment of
hypoglycemia

Recreated from Table 6.4 of the ADA Standards of Care in Diabetes – 2024

Treatment of Hypoglycemia
The preferred treatment for hypoglycemia (BG <70 mg/dL) in conscious patients is 15-20 grams of
oral glucose (or any form of fast-acting carbohydrate containing glucose). The treatment should be
repeated 15 minutes later if hypoglycemia persists.

Patients receiving insulin or those who are at a high-risk for hypoglycemia should be prescribed
glucagon (available as nasal spray and injection). A preparation that does not require reconstitution
is preferred. All patients and caregivers should be instructed on proper use.

In the event of one or more Level 2 or 3 hypoglycemic episodes, the patient’s glucose-lowering
regimen should be re-evaluated with consideration for de-intensifying therapy or switching to
agents with a lower risk for hypoglycemia.

Counsel patients on the importance of correcting hypoglycemic episodes.

• The potential risks resulting from short-term hyperglycemia are insignificant compared to the
- - - - clear risks and consequences of untreated hypoglycemia

35
References
1. American Diabetes Association Professional Practice Committee. American Diabetes Association. Standards of Care in Diabetes -
2024. Diabetes Care 1 January 2024; 47 (Supplement_1): S1–S321.

2. Lajthia E, Bucheit JD, Nadpara PA, et al. Combination therapy with once-weekly glucagon like peptide-1 receptor agonists and
dipeptidyl peptidase-4 inhibitors in type 2 diabetes: a case series. Pharm Pract (Granada). 2019;17(4):1588. doi:10.18549/
PharmPract.2019.4.1588

3. Radin MS. Pitfalls in hemoglobin A1c measurement: when results may be misleading. J Gen Intern Med. 2014;29(2):388-394.

4. Hirsch IB. Insulin analogues. N Engl J Med. 2005 Jan 13;352(2):174-83.

5. Wells BG, DiPiro JT, Schwinghammer TL, DiPiro CV. Pharmacokinetics of select insulins administered subcutaneously - Table 19-3.
Pharmacotherapy Handbook, Tenth Edition.

6. ADMELOG - insulin lispro injection, solution. Sanofi-Aventis U.S. LLC Accessed via DailyMed. Updated November 30, 2020.

7. AFREZZA - insulin human powder, metered AFREZZA - insulin human kit. Mannkind Corporation.
Accessed via DailyMed. Updated March 22, 2021.

8. APIDRA - insulin glulisine injection, solution APIDRA SOLOSTAR- insulin glulisine injection, solution.
Sanofi-Aventis U.S. LLC Accessed via DailyMed. Updated January 3, 2019.

9. BASAGLAR KWIKPEN - insulin glargine injection, solution BASAGLAR TEMPO PEN - insulin glargine injection, solution. Eli Lilly and
Company. Accessed via DailyMed. Updated September 27, 2021.

10. FIASP - insulin aspart injection injection, solution. Novo Nordisk. Accessed via DailyMed. Updated December 19, 2019.

11. HUMALOG- insulin lispro injection, solution HUMALOG KWIKPEN - insulin lispro injection, solution HUMALOG JUNIOR KWIKPEN -
insulin lispro injection, solution HUMALOG TEMPO PEN - insulin lispro injection, solution. Eli Lilly and Company.
Accessed via DailyMed. Updated May 3, 2021.

12. HUMULIN N - insulin human injection, suspension STERILE DILUENT - diluent injection, solution. Eli Lilly and Company.
Accessed via DailyMed. Updated June 27, 2022.

13. HUMULIN R - insulin human injection, solution. Eli Lilly and Company. Accessed via DailyMed. Updated June 27, 2022.

14. HUMULIN R U-500 - insulin human injection, solution HUMULIN R U-500 KWIKPEN - insulin human injection, solution.
Eli Lilly and Company. Accessed via DailyMed. Updated June 27, 2022.

15. LANTUS - insulin glargine injection, solution LANTUS SOLOSTAR - insulin glargine injection, solution. Sanofi-Aventis U.S. LLC
Accessed via DailyMed. Updated January 27, 2021.

16. LEVEMIR - insulin detemir injection, solution. Novo Nordisk. Accessed via DailyMed. Updated July 1, 2022.

17. LYUMJEV - insulin lispro-aabc injection, solution LYUMJEV KWIKPEN - insulin lispro-aabc injection, solution LYUMJEV JUNIOR
KWIKPEN - insulin lispro-aabc injection, solution LYUMJEV TEMPO PEN- insulin lispro-aabc injection, solution LYUMJEV KWIKPEN -
insulin lispro-aabc injection, solution. Eli Lilly and Company. Accessed via DailyMed. Updated August 13, 2021.

18. NOVOLOG - insulin aspart injection, solution INSULIN DILUTING MEDIUM FOR NOVOLOG - water injection injection, solution.
Novo Nordisk. Accessed via DailyMed. Updated October 22, 2021.

19. NOVOLIN N - human insulin injection, suspension. Novo Nordisk. Accessed via DailyMed. Updated November 15, 2019.

20. NOVOLIN R- human insulin injection, solution. Novo Nordisk. Accessed via DailyMed. Updated November 15, 2019.

21. SEMGLEE - insulin glargine injection, solution. Mylan Specialty L.P. Accessed via DailyMed. Updated June 8, 2020.

22. REZVOGLAR KWIKPEN- insulin glargine-aglr injection, solution. Eli Lilly and Company. Accessed via DailyMed.
Updated November 16, 2022.

23. TOUJEO - insulin glargine injection, solution TOUJEO MAX - insulin glargine injection, solution. Sanofi-Aventis U.S. LLC
Accessed via DailyMed. Updated December 3, 2020.

24. TRESIBA - insulin degludec injection, solution. Novo Nordisk. Accessed via DailyMed. Updated July 1, 2022.

25. METFORMIN HYDROCHLORIDE tablet. ACI Healthcare USA, Inc. Accessed via DailyMed. Updated December 26, 2020.

26. METFORMIN ER 500 MG tablet, METFORMIN ER 750 MG tablet. Granules India Ltd. Accessed via DailyMed. Updated April 5, 2021.

27. TRULICITY - dulaglutide injection, solution. Eli Lilly and Company. Accessed via DailyMed. Updated June 10, 2022.

28. BYETTA - exenatide injection. AstraZeneca Pharmaceuticals LP. Accessed via DailyMed. Updated June 10, 2022.

29. BYDUREON - exenatide injection, suspension, extended release BYDUREON - exenatide kit. AstraZeneca Pharmaceuticals LP.
Accessed via DailyMed. Updated July 26, 2022.

30. VICTOZA - liraglutide injection. Novo Nordisk. Accessed via DailyMed. Updated June 10, 2022.

36
References
31. ADLYXIN - lixisenatide kit ADLYXIN - lixisenatide injection solution. Sanofi-Aventis U.S. LLC
Accessed via DailyMed. Updated June 17, 2022.

32. OZEMPIC- semaglutide injection, solution. Novo Nordisk. Accessed via DailyMed. Updated March 28, 2022.

33. RYBELSUS - oral semaglutide tablet. Novo Nordisk. Accessed via DailyMed. Updated June 10, 2022.

34. MOUNJARO - tirzepatide injection, solution. Eli Lilly and Company. Accessed via DailyMed. Updated May 13, 2022.

35. INVOKANA - canagliflozin tablet, film coated. Janssen Pharmaceuticals, Inc. Accessed via DailyMed. Updated November 9, 2021.

36. FARXIGA - dapagliflozin tablet, film coated. AstraZeneca Pharmaceuticals LP. Accessed via DailyMed. Updated July 11, 2022.

37. JARDIANCE - empagliflozin tablet, film coated. Boehringer Ingelheim Pharmaceuticals, Inc. Accessed via DailyMed.
Updated March 23, 2022.

38. STEGLATRO - ertugliflozin tablet, film coated. Merck Sharp & Dohme LLC. Accessed via DailyMed. Updated May 20, 2022.

39. BRENZAVVY - bexagliflozin tablet. TheracosBio, LLC. Accessed via DailyMed. Updated September 18, 2023.

40. INPEFA - sotagliflozin tablet. Lexicon Pharmaceuticals, Inc. Accessed via DailyMed. Updated November 2, 2023.

41. NESINA - alogliptin tablet, film coated. Takeda Pharmaceuticals America, Inc. Accessed via DailyMed. Updated March 17, 2022.

42. TRADJENTA - linagliptin tablet, film coated. Boehringer Ingelheim Pharmaceuticals, Inc. Accessed via DailyMed.
Updated April 21, 2022.

43. ONGLYZA - saxagliptin tablet, film coated. AstraZeneca Pharmaceuticals LP. Accessed via DailyMed. Updated October 24, 2019.

44. JANUVIA - sitagliptin tablet, film coated. Merck Sharp & Dohme LLC. Accessed via DailyMed. Updated July 22, 2022.

45. GLIPIZIDE tablet. Mylan Pharmaceuticals Inc. Accessed via DailyMed. Updated April 7, 2022.

46. GLIPIZIDE tablet, extended release. Zydus Pharmaceuticals USA Inc. Accessed via DailyMed. Updated November 9, 2022.

47. GLIMEPIRIDE tablet. Aurobindo Pharma Limited. Accessed via DailyMed. Updated November 8, 2022.

48. GLYBURIDE tablet. Zydus Lifesciences Limited. Accessed via DailyMed. Updated November 16, 2022.

49. GLYNASE - glyburide tablet. Pharmacia and Upjohn Company LLC. Accessed via DailyMed. Updated October 7, 2017.

50. ACTOS - pioglitazone tablet. Takeda Pharmaceuticals America, Inc. Accessed via DailyMed. Updated December 16, 2021.

51. AVANDIA 2MG- rosiglitazone maleate tablet, film coated, AVANDIA 4MG- rosiglitazone maleate tablet, film coated.
GlaxoSmithKline LLC. Accessed via DailyMed. Updated November 2020.

52. American Diabetes Association. Insulin Administration. Diabetes Care 2003 Jan; 26(suppl 1): s121-s124.
https://doi.org/10.2337/diacare.26.2007.S121

53. Rehman A, Setter SM, Vue MH. Drug-Induced Glucose Alterations Part 2: Drug-Induced Hyperglycemia.
Diabetes Spectrum 2011 Nov; 24(4): 234-238.

54. Vue MH, Setter SM. Drug-Induced Glucose Alterations Part 1: Drug-Induced Hypoglycemia.
Diabetes Spectrum 2011 Aug; 24(3): 171-177.

55. Drug-induced low blood sugar. Medline Plus - U.S. National Library of Medicine. Page last updated: 04 February 2020.

56. By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers
Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372

57. Trujillo J, Haines S. Diabetes Mellitus. In: DiPiro JT, Yee GC, Haines ST, Nolin TD, Ellingrod VL, Michael Posey LL. eds. DiPiro’s
Pharmacotherapy: A Pathophysiologic Approach, 12e. McGraw Hill; 2023. Accessed January 26, 2023.

58. Patoulias D, Dimosiari A. Meta-analysis Addressing the Cardiovascular Safety of Bexagliflozin in Patients With Type 2 Diabetes
Mellitus. Am J Cardiol. 2022;178:178-179. doi:10.1016/j.amjcard.2022.05.005

59. Allegretti AS, Zhang W, Zhou W, et al. Safety and Effectiveness of Bexagliflozin in Patients With Type 2 Diabetes Mellitus and Stage
3a/3b CKD. Am J Kidney Dis. 2019;74(3):328-337. doi:10.1053/j.ajkd.2019.03.417

60. Riddle, M., & Ahmann, A. (2020). Therapeutics of Type 2 Diabetes Mellitus. In Williams Textbook of Endocrinology
(Fourteenth ed., pp. 1371-1402.e9).

61. Clinical Management Topics: Learning How to Inject Insulin. Association of Diabetes Care & Education Specialists. 2020.
Retrieved February 2, 2023.

62. Clinical Management Topics: Using GLP-1 Receptor Agonists. Association of Diabetes Care & Education Specialists. 2020.
Retrieved February 2, 2023.

63. Figures created with BioRender.com

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